CAN A TEST FOR E6 E7 TRANSCRIPTS OF HUMAN PAPILLOMAVIRUS TYPE-16 SERVE AS A DIAGNOSTIC-TOOL FOR THE DETECTION OF MICROMETASTASIS IN CERVICAL-CANCER/

Tissue from II cases of cervical cancer positive for human papillomavi rus (HPV) type 16 DNA and 69 pelvic lymph nodes from the same patients were examined for HPV 16 DNA and mRNA from the E6/E7 genes. Five of t he tumors were squamous, 3 adeno- and 3 adenosquamous carcinoma. From the primary tumors and the extirpated lymph nodes DNA and RNA or mRNA was subjected to PCR and RT-PCR, Three transcription profiles (only E6 1, E6*1 and E6*11 or full-length E6-E7 plus both of the spliced trans cripts) were found in all of the I I HPV 16 DNA-positive primary tumor s. from the total of 69 lymph nodes analyzed 28 were positive for mRNA . HPV 16 DNA was found in 7 additional samples. Cytokeratin was found in 19 of these lymph nodes, indicating epithelial origin of tumor cell s. Only I patient had 2 metastases evidenced by histology. These were both positive for HPV DNA and mRNA. The finding of HPV DNA, mRNA and c ytokeratin in lymph nodes of patients with cervical cancer should be a n indication of lymphogenically driven micrometastases of the tumor. T he HPV mRNA assay should offer higher specificity than the DNA test si nce mRNA can be found in live cells only, while HPV DNA also can origi nate from dead cell material sequestered in the lymph nodes. (C) 1995 Wiley-Liss, Inc.